Improving Quality: Anticoagulation Therapy · DVT/PE - Prophylaxis – ACCP 9th guidelines changes:...

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Improving Quality: Improving Quality: Anticoagulation TherapyAnticoagulation Therapy


Mark Wurster, MDFounder and Chief Medical Officer

Standing Stone, Inc.

Scope of the ProblemScope of the Problem• Adverse Drug Events (ADEs)

1 5 illi t bl ADE i– 1.5 million preventable ADEs in United States annually

– Anticoagulants account for 4% of preventable ADEs and 10% of potential ADEspotential ADEs.

Committee on Identifying and Preventing Medication Errors. Aspden P, Wolcott J, Bootman JL, Cronenwett LR, Editors. Preventing Medication Errors: Quality Chasm Series. Washington, DC: National Academies Press; July 2006.

Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events: Implications for prevention. ADE Prevention Study Group. JAMA. 1995;274:29-34.

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Scope of the ProblemScope of the Problem

• Adverse Drug Events (ADEs)

– Heparin and warfarin constitute 2 of the top 3 medications requiring ER visits due to complications

– Anticoagulants are frequently it d i di l l ticited in medical malpractice

litigation

Wu KW, Pantaleo N. Am J Health-Syst Pharm 60(3):253-259, 2003

Scope of the ProblemScope of the Problem• Anticoagulation remains underused

– Despite 29 studies showing efficacy of p g yanticoagulation for stroke prevention in patients with Atrial Fibrillation:

– In study of 12 stroke centers from 2003-2007,

– Less than 10% of patients were therapeutically anticoagulated

– 30% not on any anticoagulation therapy– 30% not on any anticoagulation therapy

– 61% not on warfarin; of those treated, 29% subtherapeutic

– Result: 597 pts c/ strokes; 60% disabled, 20% died

Gladstone, DJ, et al. Publication pending, Stroke 2009

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• Anticoagulation remains underused

– HCFA/CMS data: 40,000 strokes/ $600,000,000 annually could be prevented by proper use

– 1-2 million patients treated; 4-6 million patients have indications for treatmentp

– Less than half of pts on treatment are in therapeutic range


• Need for improved anticoagulationmanagement widely recognized:

– Centers for Medicare

– AHRQ

– American College of Chest Physicians

– Joint Commission

– Leapfrog Coalition

– Third party providers

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• Need for improved anticoagulation t id l i dmanagement widely recognized

– Examples from the Internet:• (google mail banner)- “www._______.com - Our

Experienced Lawyers Will Review Your Heparin Case For Free”.

• (another site)- “_______ assists attorneys evaluating cases involving anticoagulant therapy by considering the answers to these top ten questions and others applicable to the case:

Scope of the ProblemScope of the Problem1. Was the patient an appropriate candidate for

anticoagulation?

2 Did the patient comply with outpatient blood2. Did the patient comply with outpatient blood tests needed to monitorresponse to the anticoagulants?

3. Were standardized protocols used to order anticoagulation?

4. How often were clotting times tested?

5. Were abnormally elevated clotting times acted upon with dosageadjustments?

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6. Were there any signs of bleeding while the patient was on anticoagulation?

7. How quickly did the healthcare team respond to bleeding?

8. Did the nurses give Heparin or Coumadin as ordered?

9. Is there evidence that hemorrhage was the cause of the patient’scause of the patient sdeath, or was some other cause more likely?

10.What type of medical expert is most appropriate to review the case?”

• 2008 - National Patient Safety Goal 3E

Joint Commission RequirementsJoint Commission Requirements

– Reduce the likelihood of patient harm associated with the use of anticoagulation therapy.

• Full compliance required by all accredited systems as of 1/1/2009accredited systems as of 1/1/2009.

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Case #1Case #1

• 68 yo female admitted for left knee replacementreplacement

– Surgery successful; on post-op day 15, pt found dead at home

– Post mortem exam: cause of death massive pulmonary embolusmassive pulmonary embolus

– What may have happened? Was anything in this situation preventable?

DVT/PE - ProphylaxisDVT/PE - Prophylaxis

• Current ACCP guidelines - 9th Editiong

– Address what to do

– When to do it

– What to useWhat to use

– What not to use

CHEST 2012; 141(2)(Suppl):e227S–e277S453.

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• What to use – Low Molecular Weight Heparins (LMWH)Heparins (LMWH)

– Enoxaparin – 30 mg SubQ twice daily, or 40 mg SubQ daily

– Dalteparin – 2500-5000 int units SubQ dailyy

– Tinzaparin –not approved for VTE prophylaxis

GeertsGeerts, WH, et al. Prevention of Venous , WH, et al. Prevention of Venous ThromboembolismThromboembolism. . ChestChest. 2008; 133:381S. 2008; 133:381S--453.453.


• What to use – Fondaparinux

• Parenteral Factor Xa inhibitor

– Indicated for:

– DVT/PE

– VTE prophylaxis

Geerts, WH, et al. Prevention of Venous Thromboembolism. Chest. 2008; 133:381S-453.

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• What to use – Fondaparinuxp

• Dosing- varies by indication and body weight

– VTE prophylaxis: 2.5 mg SubQ daily, in pts > 50kg

– DVT/PE treatment: 5 mg SubQ daily (pts < 50kg)

7.5 mg SubQ daily (pts 50-100kg)

10 mg SubQ daily (pts > 100kg)



• What to use – Low dose unfractionated heparin (LDUH or UFH)unfractionated heparin (LDUH or UFH)

– Dosing- 5,000 units SubQ bid or tid

– Compared to LMWH, LDUH is associated with increased risk of heparin induced thrombocytopeniaheparin induced thrombocytopenia


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• What to use – Warfarin

– Dosing- varies due to medications, genetic phenotype, diet. If used for prophylaxis:

– VTE prophylaxis: INR goal should be 2 5 with acceptable INR range of 2 32.5, with acceptable INR range of 2-3.



• What to use – Rivaroxaban

– Dosing- 10 mg po daily:

– VTE prophylaxis: for hip replacement: duration is 35 days

F k l d i i 12– For knee replacement: duration is 12 days

CHEST 2012; 141(2)(Suppl):e227S–e277S453.

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DVT/PE - ProphylaxisDVT/PE - Prophylaxis• What NOT to do:

N thi id f h l i– Nothing – avoidance of prophylaxis results in avoidable morbidity and mortality

– Rely on Aspirin alone

– Rely on mechanical devices alone, unless patient has high risk of bleeding



• What TO do: Prevent the Event!

For patients undergoing:– For patients undergoing:

• Major general, gynecologic, or urologic surgery-use LMWH, unfractionated heparin (UFH) or fondaparinux

• Consider Intermittent Pneumatic Compression as adjunct


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• What to do: Prevent the Event!

For patients undergoing:


– For patients undergoing:

• Hip or knee arthroplasty, hip fx repair-use LMWH, fondaparinux, or warfarin (goal INR 2.5), for at least 10 daysleast 10 days

• Consider Intermittent Pneumatic Compression as adjunct



• What TO do: Prevent the Event!

– For patients with acute medical illness – use LMWH, UFH or fondaparinux

• Consider Intermittent Pneumatic C i dj tCompression as adjunct


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DVT/PE - ProphylaxisDVT/PE - Prophylaxis• What TO do: Prevent the Event!

Thromboproph la is is also– Thromboprophylaxis is also important for patients in the following situations:

• Intensive Care Unit

• Major trauma

• Spinal cord injury

GeertsGeerts, WH, et al. Prevention of Venous , WH, et al. Prevention of Venous ThromboembolismThromboembolism. . ChestChest. 2008; 133:381S. 2008; 133:381S--453.453.

DVT/PE - ProphylaxisDVT/PE - Prophylaxis– ACCP 9th guidelines changes:

• Post op ortho Rx duration 10 35• Post-op ortho Rx duration- 10-35 days; consider new DTI’s

• Low risk medical pts may not require Rx

• Outpts with CA but no other risks-no routine prophylaxis

CHEST 2012; 141(2)(Suppl):e278SCHEST 2012; 141(2)(Suppl):e278S––e325Se325S..CHEST 2012; 141(2)(Suppl):e278SCHEST 2012; 141(2)(Suppl):e278S––e325Se325S..

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Case #2Case #2

• 59 yo male admitted for CABG

S f l d– Surgery successful; on post-op day 5, pt c/o of sudden pain in R leg

– PE: R LE cool, c/ diminished DP pulse

L b L t BUN C WNL CBC H/H– Lab: Lytes BUN Cr WNL; CBC: H/H 9.2/29, WBC 11.5, Plts 63,000

– What may have happened?

Case #2Case #2

• Heparin Induced Thrombocytopenia

Severe adverse drug reaction to– Severe adverse drug reaction to heparin

– Caused by antibody mediated reaction

A i t d ith i ifi tl– Associated with significantly increased risk of thrombosis

Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low molecularweight heparin or unfractionated heparin. N Engl J Med 1995; 332:1330–1335

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Heparin Induced Thrombocytopenia


• Early detection is effective

– Consider regularly scheduled platelet counts (every 2-3 days) for all patients on UFH or LMWH.

– A reduction in platelet counts of greater than 50% from baseline should trigger gguse of alternative agent for anticoagulation until laboratory evaluation confirms or rules out HIT.

Franchini M. Heparin Induced Thrombocytopenia: An Update. Thrombosis Journal 2005, 3:14



• If HIT is suspected:

– Clinical suspicion is key- don’t wait for confirmation

– If suspected, immediately stop all heparin, LMWH

Start alternative agent for– Start alternative agent for anticoagulation; must not cross react with HIT associated antibodies.

Chong BH: Heparin-induced thrombocytopenia. J Thromb Haemost 2003, 1:1471-1478.


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• Treatment- alternative agents

A d t f HIT t t t ll– Approved agents for HIT treatment; all directly inhibit thrombin activity or formation

• Argatroban

• Lepirudin• Lepirudin

• Danaparoid




HIT – TreatmentHIT – Treatment• Argatroban

Dosing - initial dose is 2– Dosing - initial dose is 2 μg/kg/minute given intravenously

– Adjust dose to achieve an aPTT 1.5 to 3 times the baseline value.

– Drug of choice for patients with renal insufficiency

Franchini M. Heparin Induced Thrombocytopenia: An Update. Thrombosis Journal 2005, 3:14Chong BH: Heparin-induced thrombocytopenia. J Thromb Haemost 2003, 1:1471-1478.

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HIT – TreatmentHIT – Treatment• Danaparoid

– Dosing - intravenous bolus dose of 2500 U followed by 400 U/hour for 4 hours, then 300 U/hour for 4 hours and subsequently 200 U/hour until anticoagulation is no longer requiredq

– Adjust the dose to maintain plasmaanti-Xa levels within 0.5–0.8 U/mL.


HIT – TreatmentHIT – Treatment• Lepirudin

– Dosing - 0.4 mg/kg as a bolus f ll d b 0 15 /k /hfollowed by 0.15 mg/kg/hour

– Adjust the dose to achieve an aPTT of 1.5 to 3 times the baseline value.

– Drug of choice for patients withDrug of choice for patients with liver dysfunction, or requiring cardiac surgery


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Anticoagulation : Anticoagulation : New Guidelines andNew Guidelines andNew AnticoagulantsNew Anticoagulants

Anticoagulation : Anticoagulation : New Guidelines andNew Guidelines andNew AnticoagulantsNew Anticoagulantsgggg

Aaron Dush, PharmD, CACPSpecialty Practice Pharmacist, Anticoagulation

The Ohio State UniversityyComprehensive Cancer Center-

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

9th Edition CHEST Guidelines February 2012

9th Edition CHEST Guidelines February 2012

Wh t f th What are some of the new recommendations

What are some of the changes

How do we apply these to patient care

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Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American

College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Chest February 2012 141:2 suppl 53S

Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American


Chest February 2012 141:2 suppl 53S

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Evidence-Based Management of Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based

Clinical Practice Guidelines Chest February 2012 141:2 suppl e152S-e184S

Evidence-Based Management of Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based


2.1. For patients sufficiently healthy to be treated as outpatients, we suggest initiating Vitamin K Antagonist (VKA) therapy with warfarin 10 mg daily for the first 2 days followed by dosing based on INRfollowed by dosing based on INR measurements rather than starting with the estimated maintenance dose (Grade 2C).

Evidence-Based Management of Anticoagulant Therapy: Antithrombotic Therapy and Prevention of

Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice

Guidelines Chest February 2012 141:2 suppl e152S-e184S

Evidence-Based Management of Anticoagulant Therapy: Antithrombotic Therapy and Prevention of

Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice

Guidelines Chest February 2012 141:2 suppl e152S-e184S

3.1. For patients taking VKA therapy with consistently stable INRs, we suggest an INR testing frequency of up to 12 weeks rather than every 4 p yweeks (Grade 2B)

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Evidence-Based Management of Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical

Practice Guidelines Chest February 2012 141:2 suppl e152S-e184S



3.2. For patients taking VKAs with previously stable therapeutic INRs who present with a single out-of-range INR of ≤ 0.5 below or above therapeutic, we suggest continuing the current dosesuggest continuing the current dose and testing the INR within 1 to 2 weeks (Grade 2C).





3.3. For patients with stable therapeutic INRs presenting with a single subtherapeutic INR value, we suggest against routinely administering bridging with heparin (Grade 2C).

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9.1. (a) For patients taking VKAs with INRs between 4.5 and 10 and no evidence of bleeding, we suggest against the routine use of vitamin K (G d 2B)(Grade 2B)





(b) For patients taking VKAs with INRs > 10.0 and with no evidence of bleeding, we suggest that oral vitamin K be administered (Grade (2C).

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9 3 For patients with VKA-associated major9.3. For patients with VKA-associated major bleeding, we suggest rapid reversal of anticoagulation with four-factor PCC rather than with plasma (Grade 2C).

We suggest the additional use of vitamin K 5 ggto 10 mg administered by slow IV injection rather than reversal with coagulation factors alone (Grade 2C).

Case 1Case 1 LP is an 52 yo male with a history of

recurrent thrombotic events on chronic warfarin therapy

Patient has been stable within his desired therapeutic INR range of 2-3 on his current total weekly dose (TWD) of warfarin for 6

thmonths

Today he presents in clinic with an INR 1.6

What should be done?

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Case 1Case 1 According to the new CHEST guidelines:

– The patient’s current TWD should be continued and the patient should follow-up in 1-2 weeks

– Bridge therapy does not need to be initiated at this time

Antithrombotic Therapy for Atrial Fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American


Chest February 2012 141:2 suppl e531S-e575S




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2 1 8 For patients with AF including those with2.1.8. For patients with AF, including those with paroxysmal AF, who are at low risk of stroke (eg, CHADS2 score = 0), we suggest no therapy rather than antithrombotic therapy (Grade 2B). For patients who do choose antithrombotic therapy, we suggest aspirin (75 mg to 325 mg once daily)we suggest aspirin (75 mg to 325 mg once daily) rather than oral anticoagulation (Grade 2 B) or combination therapy with aspirin and clopidogrel (Grade 2B).







2.1.9. For patients with AF, including those with2.1.9. For patients with AF, including those with paroxysmal AF, who are at intermediate risk of stroke (eg, CHADS2 score = 1), we recommend oral anticoagulation rather than no therapy (Grade 1B). We suggest oral anticoagulation rather than aspirin (75 mg to 325 mg once daily) (Grade 2B) or combination therapy with aspirin and clopidogrel (Grade 2B). For py p p g ( )patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than concerns about major bleeding), we suggest combination therapy with aspirin and clopidogrel rather than aspirin (75 mg to 325 mg once daily) (Grade 2B).

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2.1.10. For patients with AF, including those with l AF h t hi h i k f t k (paroxysmal AF, who are at high risk of stroke (eg,

CHADS2 score ≥ 2), we recommend oral anticoagulation rather than no therapy (Grade 1A), aspirin (75 mg to 325 mg once daily) (Grade 1B), or combination therapy with aspirin and clopidogrel (Grade 1B). For patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than concerns about major bleeding), we recommend combination therapy with aspirin and clopidogrel rather than aspirin (75 mg to 325 mg once daily). (Grade 1B)







2.1.11. For patients with AF, including those with paroxysmal AF, for recommendations in favor of oral anticoagulation, we suggest dabigatran 150 mg twice daily rather than adjusted-dose VKA therapy (target INR range, 2.0 – 3.0) (Grade 2B).

Remarks: Dabigatran is excreted primarily by theRemarks: Dabigatran is excreted primarily by the kidney. It has not been studied and is contraindicated in patients with severe renal impairment (estimated creatinine clearance of ≤ 30 mL/min). Clinicians should be aware that there is no antidote for dabigatran.

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Dabigatran (Pradaxa®)PI: Pradaxa (dabigatran)oral tablets; Boehringer Ingelheim; Ridgefield, CT,

2010

Dabigatran (Pradaxa®)PI: Pradaxa (dabigatran)oral tablets; Boehringer Ingelheim; Ridgefield, CT,

2010

Direct thrombin inhibitor indicated to reduce the risk of stroke and systemic embolism in patients y pwith non-valvular atrial fibrillation

CrCl Dose

>30 mL/min 150mg BID

15-30 mL/min 75mg BID*

* Based on pharmacokinetic modeling

<15 mL/min or hemodialysis Unknown

Dabigatran (Pradaxa®)Stangier J. Clin Pharmacokinet 2008;47:285-295


Bi il bilit 6 5%Bioavailability 6.5%

tmax 1.5-3 h (healthy patients)

3.7-4.5 h (day of surgery)

Vd 60-70 L

Elimination 80% renal unchangedg

t½ 12-17 h

Protein binding 35%

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Holding for Procedures

Creatinine Clearance Hold for:

≥ 50 mL/min 1-2 days

< 50 mL/min 3-5 days

Consider holding longer for major surgery, spinal puncture,placement of spinal/epidural catheter

Dabigatran (Pradaxa®)Dabigatran (Pradaxa®)

No cytochrome P-450 activity

Interaction with P-glycoprotein

No dietary interactions

Larger Therapeutic Indexa ge e apeut c de

No monitoring recommended

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Rivaroxiban (Xarelto®)PI: Xarelto (dabigatran) oral tablets; Bayer HealthCare AG, 51368

Leverkusen, Germany

Rivaroxiban (Xarelto®)PI: Xarelto (dabigatran) oral tablets; Bayer HealthCare AG, 51368

Leverkusen, Germany

Rivaroxaban selectively inhibits factor Xa to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation and to reduce the risk of deepvalvular atrial fibrillation and to reduce the risk of deep vein thrombosis post knee and hip replacement surgery

Indication CrCl Dose

A-Fib > 50 ml/min 20 mg daily

A-Fib 15 - 50 ml/min 15 mg daily

Post-Hip Replacement 10 mg dailyPost Hip Replacement 10 mg daily

(rec. duration of 35 days)

Post- Knee Replacement

10 mg daily

(rec. duration of 12 days)

“The Ideal Anticoagulant”“The Ideal Anticoagulant”Warfarin Dabigatran Rivaroxiban

Oral dosage form

Predictable, rapid effect

Few drug interactions

Reversibility

InexpensiveInexpensive

No need for monitoring

Once daily dosing

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Other Considerations for New Anticoagulants


No reversal agentg

Adverse reactions

Still bleeding risk

Dyspepsia (35% with dabigatran)

Renal DosingRenal Dosing

Lack of monitoring



Compliance Compliance

Faster return to baseline (short half-life syndrome)

Cost

Twice daily dosing (dabigatran)

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Perioperative Management of Antithrombotic Th A tith b ti Th dTherapy: Antithrombotic Therapy and

Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based

Clinical Practice Guidelines

Chest February 2012 141:2 suppl e326S-Chest February 2012 141:2 suppl e326Se350S

Case 2Case 2 JP is a 49yo female

Thrombosis of the main portal vein May 2011,

Rescanned February 2012 still showing portal vein Rescanned February 2012 still showing portal vein thrombosis.

Hx of stage I ER/PR positive breast cancer.

Mastectomy and sentinel lymph node biopsy was performed on 01/30/2008

No findings on Mammogram December 2011 No findings on Mammogram December 2011.

Adjuvent hormone therapy with tamoxifen March 2008-May 2011. Changed to letrozole May 2011.

Thrombosis risk tamoxifen vs. letrozole (1.7% vs 1.1%)

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Case 2Case 2

Patient having laparoscopic surgery for small recurrent ventral hernia

How do we handle her anticoagulation?

First question – When do we stop her anticoagulation?

First question – When do we stop her anticoagulation?

How long prior to her procedure should her How long prior to her procedure should her warfarin be stopped?

If bridged – when should her bridge therapy be stopped?

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Perioperative Management of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical




2.1. In patients who require temporary interruption of a VKA before surgery, we recommend stopping VKAs approximately 5 days before surgery instead of stopping VKAs a shorterinstead of stopping VKAs a shorter time before surgery (Grade 1C).





4.3. In patients who are receiving bridging anticoagulation with therapeutic-dose SC LMWH, we suggest administering the last preoperative dose of LMWH approximately 24 hours before surgery instead of 1224 hours before surgery instead of 12 hours before surgery (Grade 2C).

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What is the patients risk of a recurrent thrombotic event?

What is the patients risk of a recurrent thrombotic event?

High Riskg

Moderate Risk

Low Risk





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High Risk Patientsg s at e ts2.4. In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during interruption of VKA therapy (Grade 2C).

Remarks: Patients who place a higher value on avoiding perioperative bleeding than on avoiding perioperative thromboembolism are likely to decline heparin bridging.

Perioperative Management of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based




Low Risk PatientsLow Risk Patients

In patients with a mechanical heart valve, atrial fibrillation, or VTE at low risk for thromboembolism, we suggest no-bridging instead of bridging g g g ganticoagulation during interruption of VKA therapy (Grade 2C).

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Moderate Risk PatientsModerate Risk Patients

In patients with a mechanical heart valve, atrial fibrillation, or VTE at moderate risk for thromboembolism, the bridging or no-bridging approach chosen is, as in the higher- and lower-risk patients, based on an assessment of individual patient- and surgery-related factors.





Moderate Risk – Who do we consider bridge therapy?

•Patients with a mechanical bileaflet aortic valve and additional stroke risk factors comprising prior stroke or systemic embolism or transient ischemic attack, hypertension, diabetes, congestive heart failure, or age > 75 years

•Patients with atrial fibrillation and a CHADS2 score of 3 or 4 or i th b b li d i i t ti f f i

Answer: All Moderate Risk patients should be considered for bridge therapy

prior thromboembolism during interruption of warfarin

•Patients with VTE within the past 3 to 12 months, nonsevere thrombophilia, active cancer, and recurrent VTE

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Other considerations

High-bleeding-risk procedures

Renal function

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What dose of Low-Molecular-Weight-gHeparin (LMWH) do we use to bridge?

No published randomized, controlled trials on bridge therapy

In observational studies high-risk patients typically received therapeutic dose LMWH

BRIDGE Study

Prevention of VTE in Nonsurgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American



Prevention of VTE in Nonsurgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American



4.2.2. In outpatients with solid tumors who have additional risk factors for VTE and who are at low risk of bleeding, we suggest prophylactic-dose LMWH or LDUH over no prophylaxis (Grade 2B).

Remarks: Additional risk factors for venousRemarks: Additional risk factors for venous thrombosis in outpatients with cancer include previous venous thrombosis, immobilization, hormonal therapy, angiogenesis inhibitors, thalidomide, and lenalidomide

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What do we do with our patient

What do we do with our patient

What risk category does she fall in? What risk category does she fall in?

What other risk factors does she possess?

What is the bleeding risk for this patient’s procedure?

What was decidedWhat was decided

After discussion with the patient’s Oncologist, it was determined to bridge this patient with enoxaparin

Deemed patient was moderate risk

Acute event 3-12 months ago

Recent scan showing chronic thrombus

Patient is on hormonal therapy

Bleeding risk deemed low for procedure

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What about post-procedure?What about post-procedure?

When do we restart the patients warfarin th ?therapy?

When do we restart the patient’s bridge therapy?





2.2. In patients who require temporary interruption of a VKA before surgery, we recommend resuming VKAs approximately 12 to 24 hours after surgery (evening of or next morning) and when there is adequate hemostasiswhen there is adequate hemostasis instead of later resumption of VKAs (Grade 2C).

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4 4 In patients who are receiving bridging4.4. In patients who are receiving bridging anticoagulation with therapeutic-dose SC LMWH and are undergoing high-bleeding-risk surgery, we suggest resuming therapeutic-dose LMWH 48 to 72 hours after surgery instead of resuming LMWH within 24 hours after surgery (Grade 2C). In patients who are receiving bridging anticoagulation with therapeutic dose SCbridging anticoagulation with therapeutic-dose SC LMWH and are undergoing non-high-bleeding-risk surgery, we suggest resuming therapeutic-dose LMWH approximately 24 hours after surgery instead ofresuming LMWH more than 24 hours after surgery.

Summary of Bridge Therapy

Summary of Bridge Therapy

Bridging guidelines still vagueBridging guidelines still vague

Still no published randomized, controlled clinical trials with bridge therapy (BRIDGE Study ongoing)

Each patient still needs assessed individually

Guidelines will not encompass all patients and all patient risk factors

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Mark Wurster, MDFounder and Chief Medical Officer

Standing Stone, Inc.

The New AgentsThe New Agents• Unresolved issues –

• ‘Short half-life syndrome’

• Emergency reversal

• Drug/Treatment costs

• Efficacy of outcomes vs. AC carey

• Post marketing surveillance will be crucial

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DabigatranDabigatran• Pradaxa (Dabigatran)- current

situation

• Numerous case reports of complications are being reported in US, New Zealand, Australia

• In December 2011, FDA requested additional information from physicians regarding PradaxaPradaxa

• Case reports are limited in terms of information gained, especially in terms of relative risk compared to other therapeutic options

The New Agents- Clinical UseThe New Agents- Clinical Use• Dabigatran Case Series – A

prospective, observational cohort st dstudy

• Purpose-

• To evaluate the clinical outcomes of patients receiving anticoagulationpatients receiving anticoagulation therapy with dabigatran, using warfarin therapy as a comparison

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Dabigatran Case SeriesDabigatran Case Series• Setting-

• Staten Island / Long Island Jewish hospital-

• Anticoagulation clinic currently follows approximately 2200 patients,follows approximately 2200 patients, the majority of which are POC testers

Dabigatran Case SeriesDabigatran Case Series• Design-

• Beginning 11/2010, all patients switched from warfarin to dabigatran followed prospectively for one year, with retrospective chart reviews covering one year prior while on warfarin

• Cohort design allows each patient to serve as Co o t des g a o s eac pat e t to se e astheir own control

• Endpoints- bleeds, thromboses, or other Rx complications that required med to be D/C’ed

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Dabigatran Case SeriesDabigatran Case Series

• Design-

• Endpoints- bleeds, thromboses, or other treatment related complications that required medication to be discontinuedmedication to be discontinued

• Results were compared by means of Fisher’s exact test


• Preliminary Results-

• For 113 eligible patients after 6 months of warfarin therapy, followed by 6 months of dabigatran therapy:

• For almost all patients, reasons listed for switching therapy included physician orswitching therapy included physician or patient convenience; in one case, a patient who planned to be overseas needed an alternative to regular INR monitoring

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• During warfarin treatment phase, one patient was admitted to the hospital for diagnosis of ‘warfarin t i it ’toxicity’


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Events Requiring Medication Stoppage

4

6

8

10

12

14

# of Events (p <0.0014)

0

2

Warfarin Treatment

Phase

Dabigatran Treatment

Phase

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Dabigatran Case SeriesDabigatran Case SeriesOther (skin rash)8%

Frequency of Dabigatran Complications by Type

Hemorrhage38%

GastroIntestinal Sx

31%

8%

Thrombosis23%

number of events = 13



• During dabigatran treatment phase: one death (GI bleed), four other bleeding episodes (two GI bleeds, one rectus sheath hemorrhage, one intracranial h h ) D Vhemorrhage), one Deep Venous Thrombosis, one atrial thrombus, one Transient Ischemic Attack, one skin rash, and four GI reactions

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Dabigatran Case SeriesDabigatran Case Series• Preliminary Results

• Incidence of endpoints during warfarin therapy phase was 0.83%

• Incidence of endpoints during dabigatran therapy phase was 11.5 %

• The difference was HIGHLY statistically significant

• (p < 0.0014)

• Relative risk of adverse event with dabigatran = 13.8


• Preliminary Results

• Why are the differences so striking, compared to prior studies?

• Sampling error?

• ‘Usual care’ versus study related close observation?

• Use in inappropriate subjects?

• Poor warfarin use in prior studies (TTR in RE-LY was 64% with huge variation internationall,y compared to 70% for warfarin clinic in this study)

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Dabigatran Case SeriesDabigatran Case Series• The current study is still active –

• Goals for final report – continueGoals for final report continue observation of patients for a further 6 months, with emphasis on:

• Demographics

• Renal Function

• Co morbidities• Co-morbidities

• Concomitant medications

• Other possible factors that may influence appropriate patient selection for the medication

Improving Quality: Anticoagulation Therapy · DVT/PE - Prophylaxis – ACCP 9th guidelines changes:...

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